The Expanding Role of Diazirines in Synthetic Methodology

Diazirines are three‐membered nitrogen‐containing heterocycles best known as photochemical carbene precursors in photoaffinity labeling. Upon irradiation, diazirines undergo nitrogen extrusion to generate highly reactive carbenes capable of covalent bond insertion, a property that has been widely exploited in chemical biology and materials science. Despite their favorable handling properties compared to related diazo compounds and their versatility as both carbene precursors and nitrogen sources, diazirines have historically seen only limited application in synthetic organic chemistry. Over the past two decades, however, diazirines have increasingly emerged as valuable synthons in a broad range of transformations. Their applications can generally be divided into reactions exploiting either their carbene‐generating properties or their ability to serve as nitrogen‐transfer reagents. Diazirines have been employed in cyclopropanation and cyclopropenation reactions, cross‐couplings, skeletal editing, glycosylations, reductive aminations, and the synthesis of nitrogen‐containing heterocycles. Owing to their unique reactivity, diazirines can facilitate unusual or otherwise difficult‐to‐access transformations in organic synthesis. This review provides a comprehensive overview of diazirine‐based synthetic methodologies, with particular emphasis on developments reported over the last two decades, and highlights future opportunities for their application in organic synthesis.